scholarly journals Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weng Sheng Kong ◽  
Naohiro Tsuyama ◽  
Hiroko Inoue ◽  
Yun Guo ◽  
Sho Mokuda ◽  
...  

AbstractBreastfeeding influences the immune system development in infants and may even affect various immunological responses later in life. Breast milk provides a rich source of early nutrition for infant growth and development. However, the presence of certain compounds in breast milk, related to an unhealthy lifestyle or the diet of lactating mothers, may negatively impact infants. Based on a cohort study of atopic dermatitis (AD), we find the presence of damage-associated molecular patterns (DAMPs) activity in the mother’s milk. By non-targeted metabolomic analysis, we identify the long-chain saturated fatty acids (LCSFA) as a biomarker DAMPs (+) breast milk samples. Similarly, a mouse model in which breastfed offspring are fed milk high in LCSFA show AD onset later in life. We prove that LCSFA are a type of damage-associated molecular patterns, which initiate a series of inflammatory events in the gut involving type 3 innate lymphoid cells (ILC3s). A remarkable increase in inflammatory ILC3s is observed in the gut, and the migration of these ILC3s to the skin may be potential triggers of AD. Gene expression analysis of ILC3s isolated from the gut reveal upregulation of genes that increase ILC3s and chemokines/chemokine receptors, which may play a role in ILC migration to the skin. Even in the absence of adaptive immunity, Rag1 knockout mice fed a high-LCSFA milk diet develop eczema, accompanied by increased gut ILC3s. We also present that gut microbiota of AD-prone PA milk-fed mice is different from non-AD OA/ND milk-fed mice. Here, we propose that early exposure to LCSFAs in infants may affect the balance of intestinal innate immunity, inducing a highly inflammatory environment with the proliferation of ILC3s and production of interleukin-17 and interleukin-22, these factors may be potential triggers or worsening factors of AD.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Ziomkiewicz ◽  
Magdalena Babiszewska ◽  
Anna Apanasewicz ◽  
Magdalena Piosek ◽  
Patrycja Wychowaniec ◽  
...  

AbstractWe studied a sample of 146 Polish, exclusively breastfeeding mothers and their healthy born on time infants to explore the effect of perinatal psychosocial stress on breast milk composition. Maternal perinatal stress was assessed using Recent Life Changes Questionnaire summarizing stressful events from the previous six months. Stress reactivity was determined by administering the cold pressor test and measuring cortisol in saliva samples taken during the test. Breast milk sample was taken to measure energy, protein, fat, lactose, and fatty acid content. Analyses revealed that stress reactivity was positively associated with milk fat and long-chain unsaturated fatty acids and negatively associated with milk lactose. Perinatal psychosocial stress negatively affected energy density, fat as well as medium-chain and long-chain saturated fatty acids in milk. These results, together with previous studies, advocate monitoring maternal psychological status during the peripartum to promote breastfeeding and healthy infant nutrition.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Amanda Fretts ◽  
Fumiaki Imamura ◽  
Chaoyu Yu ◽  
Alexis C Frazier-Wood ◽  
Maria Lankinen ◽  
...  

Background: Circulating saturated fatty acids are biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. Unlike palmitic acid (16:0), which has been extensively studied, little is known of the relationship of very long-chain saturated fatty acids (VLSFAs), with 20 carbons or more, to diabetes risk. Objective: To investigate the associations of circulating levels of VLSFA with incident diabetes. Methods: A meta-analysis was conducted within a consortium of prospective (cohort or nested case-control) studies having circulating measures of one or more VLSFAs, including arachidic acid (20:0), behenic acid (22:0) and lignoceric acid (24:0). Standardized analysis was conducted in each study using pre-specified models, exposures, outcomes, and covariates. Study-specific estimates were pooled using fixed effects meta-analysis. Results: Current findings were based on 9 participating studies, including 46,549 total participants and 13,750 incident diabetes. In multivariable-adjusted analyses, higher levels of all 3 VLSFAs were associated with lower risk of incident diabetes. Pooled RRs (95% CI) per interquintile range were 0.80 (0.71-0.90) for 20:0; 0.83 (0.76-0.91) for 22:0; and 0.70 (0.63-0.79) for 24:0, after adjustment for demographics, lifestyle factors and clinical conditions. Additional adjustments for circulating palmitic acid and triglyceride levels moved the RRs toward the null (illustrated for 24:0, in model 3 of the Figure ). Conclusions: Based on meta-analysis of results from several studies around the world, biomarker levels of VLSFA are associated with lower risk of incident diabetes, potentially mediated by effects on circulating triglycerides and 16:0.


2014 ◽  
Vol 457 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Marthe H. R. Ludtmann ◽  
Plamena R. Angelova ◽  
Ying Zhang ◽  
Andrey Y. Abramov ◽  
Albena T. Dinkova-Kostova

Transcription factor Nrf2 affects fatty acid oxidation; the mitochondrial oxidation of long-chain (palmitic) and short-chain (hexanoic) saturated fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively activated, affecting ATP production and FADH2 utilization.


2020 ◽  
Vol 9 (4) ◽  
Author(s):  
Paul N. Jensen ◽  
Amanda M. Fretts ◽  
Andrew N. Hoofnagle ◽  
Colleen M. Sitlani ◽  
Barbara McKnight ◽  
...  

Background Ceramides exhibit multiple biological activities that may influence the pathophysiological characteristics of atrial fibrillation (AF). Whether the length of the saturated fatty acid carried by the ceramide or their sphingomyelin precursors are associated with AF risk is not known. Methods and Results Among 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow‐up. We examined 8 sphingolipid species: ceramide and sphingomyelin species with palmitic acid and species with very‐long‐chain saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses, ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk (ie, per 2‐fold higher ceramide with behenic acid hazard ratio, 0.71; 95% CI, 0.59–0.86; sphingomyelin with behenic acid hazard ratio, 0.60; 95% CI, 0.46–0.77). In contrast, ceramides and sphingomyelins with palmitic acid were associated with increased AF risk (ceramide with palmitic acid hazard ratio, 1.31; 95% CI, 1.03–1.66; sphingomyelin with palmitic acid hazard ratio, 1.73; 95% CI, 1.18–2.55). Associations were attenuated with adjustment for NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of coronary heart disease. Conclusions Our findings suggest that several ceramide and sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the fatty acid. Ceramides and sphingomyelins with palmitic acid were associated with increased AF risk, whereas ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk.


2004 ◽  
Vol 34 (2) ◽  
pp. 194-200 ◽  
Author(s):  
R. M. Stoney ◽  
R. K. Woods ◽  
C. S. Hosking ◽  
D. J. Hill ◽  
M. J. Abramson ◽  
...  

2009 ◽  
Vol 284 (48) ◽  
pp. 33296-33304 ◽  
Author(s):  
Biju K. Pillai ◽  
Ravi Jasuja ◽  
Jeffrey R. Simard ◽  
James A. Hamilton

1997 ◽  
Vol 77 (4) ◽  
pp. 621-643 ◽  
Author(s):  
Christine A. Mattacks ◽  
Caroline M. Pond

The effects of diet on the composition and properties of adipose tissue in relation to lymph nodes were studied in adult guinea-pigs. The proportions of monoenoic triacylglycerol fatty acids were constant in all sites in adipose tissue of similarly fed guinea-pigs, but were substantially greater in samples from guinea-pigs fed on suet-enriched chow. Triacylglycerols in adipose tissue from near nodes contained significantly fewer saturated fatty acids, and significantly more 18:2n−6 and 18:3n−3 than those in samples from sites remote from nodes within the same depot. Depots that interact most strongly with lymphoid cellsin vitrohad the largest and most consistent within-depot differences. The gradients of triacylgiycerol fatty acid composition with distance from lymph nodes in two small intermuscular depots were similar in guinea-pigs fed on plain or suet-enriched chow. These findings are consistent with the hypothesis that adipose tissue around lymph nodes is specialized for local interactions with the lymphoid cells therein, and help to explain the variability of serial or duplicate measurements of adipose tissue composition. When cultured alone, lipopolysaccharide-stimulated lymph node lymphoid cells from suet-fed guinea-pigs incorporated as much labelled thymidine as the controls. Adipose tissue explants from suet-fed guinea-pigs inhibited lymphocyte proliferation much less than those of the controls, although the site-specific differences were similar. The pattern of site-specific differences in glycerol released from explants incubated alone was generally similar for both dietary groups, but except in the popliteal depot, the increases following co-culturing with lymphoid cells were smaller for samples from suet-fed guinea-pigs. These experiments show that minor changes in the fatty acid composition of the diet can substantially alter the interactions between adipose tissue and lymphoid cells.


Pathology ◽  
1983 ◽  
Vol 15 (1) ◽  
pp. 103
Author(s):  
A.J. Fellenberg ◽  
A.C. Pollard ◽  
A. Poulos ◽  
P. Sharp

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